AsianScientist (Oct. 11, 2016) – Researchers in Hong Kong have shown that a compound used in traditional Chinese medicine can be used to improve the response of patients with a particularly aggressive form of leukemia. Their results have been published in Science Translational Medicine.
Homoharringtonine (HHT), or omacetaxine mepesuccinate, is a drug that has been approved for the treatment of drug-resistant chronic myeloid leukemia. It is derived from the Japanese plum-yew (Cephalotaxus harringtonii) and was first recognized as an anti-cancer agent several decades ago by Chinese scientists.
For a subset of leukemia patients carrying an internal tandem duplication of the fms-like tyrosine kinase 3 gene (FLT3-ITD), treatment with the existing tyrosine kinase inhibitor drugs is often ineffective. In search of a way to improve the treatment outcomes for FLT3-ITD patients, a team of researchers led by Professor Anskar Yu Hung Leung at the University of Hong Kong screened a panel of 25 drugs using cells from patients with acute myeloid leukemia.
The screen identified HHT as particularly effective against FLT3-ITD, a finding which was confirmed with subsequent in vitro experiments as well as experiments in mice. Encouraged by these positive results, Leung and his team conducted a Phase II clinical study to assess the effects of HHT as an adjust to conventional treatment with a a tyrosine kinase inhibitor called sorenafib.
“20 out of 24 patients showed clearance of cancer cells from blood and bone marrow, while five patients were successfully bridged to allogeneic stem cell therapy,” Leung told Asian Scientist Magazine.
The researchers went on to show that the synergistic effect of combining HHT with sorenafib was due to the effects of HHT on protein synthesis.
“As the FLT3 protein is very short-lived, it is most sensitive to protein synthesis inhibition. Therefore, sorafenib in combination with HHT were able to achieve synergism,” Leung explained.
Noting that the drug screening platform they developed can be used to identify novel therapeutic agents and biomarkers for other subtypes of leukemia, Leung hopes that their study will lead to the design of better clinical trials and more personalized drug treatments.
The article can be found at: Lam et al. (2016) Homoharringtonine (Omacetaxine mepesuccinate) as an Adjunct for FLT3-ITD Acute Myeloid Leukemia.
Copyright: Asian Scientist Magazine; Photo: Anskar Leung.
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